Antinociceptive effects of Salvia divinorum and bioactive salvinorins in experimental pain models in mice

• Published in: Journal of ethnopharmacology 2020-02, Vol.248, p.112276-112276, Article 112276
• Main Authors: Tlacomulco-Flores, Lorenzo Leonel, Déciga-Campos, Myrna, González-Trujano, María Eva, Carballo-Villalobos, Azucena Ibeth, Pellicer, Francisco
• Format: Article
• Language: English
• Subjects: Analgesics - therapeutic use; Animals; Disease Models, Animal; Diterpenes, Clerodane - therapeutic use; Female; Male; Mice; Nociception; Opioids; Pain - drug therapy; Plant Leaves; Receptor, Serotonin, 5-HT1A - physiology; Receptors, Opioid - physiology; Salvia; Salvia divinorum epling & Játiva; Salvinorins; Serotonin
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2019.112276

Salvia divinorum Epling & Játiva is a Mexican plant used not only in rituals but also in traditional medicine for pain relief. One of the most known bioactive compounds is salvinorin A, which acts centrally in kappa-type opioid receptors. Despite its traditional use as a medicinal plant, there is not enough scientific investigation to reinforce its potential as analgesic. In this study, Salvia divinorum antinociceptive activity was evaluated in experimental models of nociceptive pain; the writhing test and formalin-induced licking behavior in mice. Different Salvia divinorum extracts were prepared by maceration at room temperature in increased polarity (hexane, ethyl acetate and methanol). The ethyl acetate extract (EAEx) was chosen in order to be fractioned and to obtain a mixture of salvinorins. The antinociceptive effect of EAEx (3, 10, 30, and 100 mg/kg, i.p.) was compared with that of tramadol (a partial opioid agonist analgesic drug, 30 mg/kg, i.p.) and the mixture of salvinorins (30 mg/kg, i.p.). In addition, a participation of opioids (naloxone, NX 1 and/or 3 mg/kg, i.p.) and serotonin 5-HT1A receptors (WAY100635, 0.32 mg/kg, i.p.) was investigated as possible inhibitory neurotransmission involved. As a result, the EAEx produced significant and dose-dependent antinociceptive effect concerning salvinorins constituents. This effect was blocked in the presence of NX and WAY100635 in the abdominal test, but only by NX in the formalin-induced licking behavior. Whereas, the effect of salvinorins mixture involved opioids and serotonin 5-HT1A receptors. Data provide evidence of the potential of this species, where salvinorin A is in part responsible bioactive constituent involving participation of the opioids and/or 5-HT1A serotonin receptors depending on the kind of pain model explored. [Display omitted]